Abstract
BackgroundThe protein Zelda was shown to play a key role in early Drosophila development, binding thousands of promoters and enhancers prior to maternal-to-zygotic transition (MZT), and marking them for transcriptional activation. Recently, we showed that Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters. Intriguingly, some Zelda sites still maintain these chromatin patterns in Drosophila embryos lacking maternal Zelda protein. This suggests that additional Zelda-like pioneer factors may act in early fly embryos.ResultsWe developed a computational method to analyze and refine the chromatin landscape surrounding early Zelda peaks, using a multichannel spectral clustering. This allowed us to characterize their chromatin patterns through MZT (mitotic cycles 8–14). Specifically, we focused on H3K4me1, H3K4me3, H3K18ac, H3K27ac, and H3K27me3 and identified three different classes of chromatin signatures, matching “promoters,” “enhancers” and “transiently bound” Zelda peaks. We then further scanned the genome using these chromatin patterns and identified additional loci—with no Zelda binding—that show similar chromatin patterns, resulting with hundreds of Zelda-independent putative enhancers. These regions were found to be enriched with GAGA factor (GAF, Trl) and are typically located near early developmental zygotic genes. Overall our analysis suggests that GAF, together with Zelda, plays an important role in activating the zygotic genome.ConclusionsAs we show, our computational approach offers an efficient algorithm for characterizing chromatin signatures around some loci of interest and allows a genome-wide identification of additional loci with similar chromatin patterns.
Highlights
The process of transcription is vital to all living organisms, and is tightly regulated by multiple mechanisms, including the packaging of DNA into chromatin
To identify additional Zelda-like regulators that act as pioneer factors during early Drosophila development, we begin by characterizing the chromatin landscape induced around early Zelda sites
We have previously shown that early Zelda peaks, identified via ZLD ChIP-seq in hand-sorted fly embryos from mitotic cycle 8, are associated with open chromatin regions and transcription factors binding later on, towards the end of the Maternal-to-Zygotic Transition (Figure 1) (Li et al 2008, Macarthur et al 2009, Harrison et al 2011)
Summary
The process of transcription is vital to all living organisms, and is tightly regulated by multiple mechanisms, including the packaging of DNA into chromatin. The DNA is wrapped around nucleosomes to form chromatin This packaging is used differentially to control in what conditions and cell types a gene is more accessible - and active and in which conditions it is tightly packed and silenced. This packaging of DNA was shown to be mediated by various mechanisms, including the deposition of covalent modifications (e.g. acetylation, methylation, phosphorylation or ubiquitylation) at different residues of the core histone proteins, that are assembled into a nucleosome (Kouzarides 2007). Who regulates packaging? Or how does the genome get packed initially in the proper architecture, e.g. to drive early developmental expression?
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